Chemical structure

Related Biological Data

Related Biological Data

Related Biological Data

Biological Activity

THZ1 is an irreversible, potent and selective inhibitor of CDK7(cyclin-dependent kinase 7) with an IC50 value of 3.2 nM.

Targets

CDK7

IC50

3.2 nM

Protocol

Cell experiment: [1]

Cell lines

Jurkat and Loucy T-ALL cell lines

Preparation method

The solubility of this compound in DMSO is <10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

THZ1 exhibited efficacy in a bioluminescent xenografted mouse model using the human T-ALL cell-line KOPTK1 when dosed twice daily at 10mg/kg. THZ1waswell tolerated at these doseswith no observable body weight loss or behavioural changes, suggesting that it caused no overt toxicity in the animals.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

As an inhibitor of CDK7, THZ1 inhibits the phosphorylation of the C-terminal domain of RNAP polymerase II, effecting the regulation of transcription. THZ1 also inhibits the activation of the CDK proteins. It is reported to disrupt the CDK7 signalling pathways both in Jurkat cells and Loucy cells. THZ1 shows a broad-based activity with IC50 values less than 200nM in a variety of cancer cell lines. Among these cell lines, T-ALL is exceptional sensitivity to THZ1 due to the transcription effect of RUNX1 caused by THZ1 [1].